The studies in this proposal will examine the effect of extrinsic factors on axonal regeneration within the central nervous system (CNS). The hypothesis to be tested is that cellular and extracellular constituents within the CNS may either facilitate axonal regeneration in some instances or limit regeneration in others. One objective of the proposed research is to characterize the regenerative ability of frog spinal cord axons and examine how this ability may be influenced by the glial and other cell types in this region. Following transection of the spinal cord or crush of dorsal root fibers, the outgrowth behavior of individual regenerating dorsal root axons stained with the horseradish peroxidase method (HRP- anterograde filling) will be studied with the light microscope and the immediate tissue environment of the same axons will be studied ultrastructurally. The effect of extrinsic factors on axonal regeneration will be examined in other experiments where an axon population with known regenerative ability (frog retinal ganglion cell axons) will be transplanted to the frog spinal cord where axonal regeneration is reported to be minimal. After axons from transplanted eyes have grown into and extended along spinal cord pathways, the cord will be transected and the ability of the severed retinal fibers to regenerate through or around the lesion will be studied by anterograde HRP filling and electron microscopy. This study will permit a direct examination of the influence of apparently adverse environmental factors on axonal outgrowth from cells normally capable of extensive regeneration after axotomy. In another series of experiments, frog optic nerve astrocytes or neuroepithelial cells will be grafted between the cut ends of the spinal cord in adult frogs to test the ability of glial or ependymal terrains to stimulate regeneration of spinal axons which ordinarily exhibit abortive outgrowth. In a second group of experiments, the presence, nature and distribution of extracellular material (i.e. GAGs) in frog optic nerve and spinal cord and the relationship between these components and axonal elongation will be examined by cytochemical and electron microscopic methods. Finally, the nature and extent of the retrograde response of optic nerve and spinal cord axons and neurons to axotomy will be examined and correlated with the respective regenerative potentials in these CNS regions.